Novel mechanism regulating endothelial permeability via T-cadherin-dependent VE-cadherin phosphorylation and clathrin-mediated endocytosisReport as inadecuate




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Molecular and Cellular Biochemistry

, Volume 387, Issue 1–2, pp 39–53

First Online: 18 October 2013Received: 01 August 2013Accepted: 09 October 2013DOI: 10.1007-s11010-013-1867-4

Cite this article as: Semina, E.V., Rubina, K.A., Sysoeva, V.Y. et al. Mol Cell Biochem 2014 387: 39. doi:10.1007-s11010-013-1867-4

Abstract

T-cadherin is a unique member of the cadherin superfamily of adhesion molecules. In contrast to -classical- cadherins, T-cadherin lacks transmembrane and cytoplasmic domains and is anchored to the cell membrane via a glycosilphosphoinositol moiety. T-cadherin is predominantly expressed in cardiovascular system. Clinical and biochemical studies evidence that expression of T-cadherin increases in post-angioplasty restenosis and atherosclerotic lesions—conditions associated with endothelial dysfunction and pathological expression of adhesion molecules. Here, we provide data suggesting a new signaling mechanism by which T-cadherin regulates endothelial permeability. T-cadherin overexpression leads to VE-cadherin phosphorylation on Y731 β-catenin-binding site, VE-cadherin clathrin-dependent endocytosis and its degradation in lysosomes. Moreover, T-cadherin overexpression results in activation of Rho GTPases signaling and actin stress fiber formation. Thus, T-cadherin up-regulation is involved in degradation of a key endothelial adhesion molecule, VE-cadherin, resulting in the disruption of endothelial barrier function. Our results point to the role of T-cadherin in regulation of endothelial permeability and its possible engagement in endothelial dysfunction.

KeywordsT-cadherin VE-cadherin Endothelial permeability Rho GTPases AbbreviationsGPIGlycosilphosphoinositol

T-cadT-cadherin

si-T-cadSuppression of native T-cadherin

Electronic supplementary materialThe online version of this article doi:10.1007-s11010-013-1867-4 contains supplementary material, which is available to authorized users.

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Author: Ekaterina V. Semina - Kseniya A. Rubina - Veronika Yu. Sysoeva - Pavel N. Rutkevich - Natalia M. Kashirina - Vsevolod A

Source: https://link.springer.com/







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